PPIAL4A

Summary

PPIAL4A (peptidylprolyl isomerase A like 4A, HGNC:24369) is a protein-coding gene on chromosome 1p11.2, encoding Peptidyl-prolyl cis-trans isomerase A-like 4A (Q9Y536). PPIases accelerate the folding of proteins. It is a selective cancer dependency (DepMap: 60.0% of cell lines).

Predicted to enable cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding. Located in extracellular exosome.

Source: NCBI Gene 653505 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• Cancer dependency (DepMap): dependent in 60.0% of screened cell lines
• MANE Select transcript: NM_001143883

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24369
Approved symbol	PPIAL4A
Name	peptidylprolyl isomerase A like 4A
Location	1p11.2
Locus type	gene with protein product
Status	Approved
Aliases	COAS2
Ensembl gene	ENSG00000263353
Ensembl biotype	protein_coding
Entrez	653505

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000577856

RefSeq mRNA: 1 — MANE Select: NM_001143883 NM_001143883

CCDS: CCDS76197

Canonical transcript exons

ENST00000577856 — 1 exons

Exon	Start	End
ENSE00003926816	120889771	120890530

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 77.84.

Top tissues by expression

90 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.84	silver quality
ventricular zone	UBERON:0003053	52.59	gold quality
duodenum	UBERON:0002114	47.99	gold quality
granulocyte	CL:0000094	45.34	silver quality
bone marrow	UBERON:0002371	45.09	gold quality
stromal cell of endometrium	CL:0002255	44.90	gold quality
bone marrow cell	CL:0002092	43.94	gold quality
vermiform appendix	UBERON:0001154	43.70	gold quality
ganglionic eminence	UBERON:0004023	43.07	gold quality
colonic epithelium	UBERON:0000397	42.03	gold quality
placenta	UBERON:0001987	38.57	gold quality
cerebellum	UBERON:0002037	37.17	silver quality
cerebellar cortex	UBERON:0002129	36.99	silver quality
lymph node	UBERON:0000029	36.90	gold quality
cerebellar hemisphere	UBERON:0002245	36.80	silver quality
cortical plate	UBERON:0005343	36.47	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
primary visual cortex	UBERON:0002436	33.24	gold quality
liver	UBERON:0002107	32.96	gold quality
prefrontal cortex	UBERON:0000451	32.25	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
blood	UBERON:0000178	30.81	silver quality
islet of Langerhans	UBERON:0000006	30.70	gold quality
right lobe of thyroid gland	UBERON:0001119	28.88	gold quality
frontal cortex	UBERON:0001870	28.72	gold quality
monocyte	CL:0000576	28.26	gold quality
nucleus accumbens	UBERON:0001882	28.14	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	27.88	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting PPIAL4A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4764-3P	96.81	67.94	580
HSA-MIR-3622B-5P	94.62	64.58	835
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• CyPA mediates the ox-LDL-induced activation and apoptosis in RAW264.7 cells by regulating autophagy. (PMID:28038796)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppifa	ENSDARG00000007409
danio_rerio	ppiaa	ENSDARG00000009212
danio_rerio	ppiab	ENSDARG00000103994
drosophila_melanogaster	Cyp40	FBGN0036020
drosophila_melanogaster	Moca-cyp	FBGN0039581
caenorhabditis_elegans		WBGENE00000877
caenorhabditis_elegans		WBGENE00000878
caenorhabditis_elegans		WBGENE00000879
caenorhabditis_elegans		WBGENE00000883
caenorhabditis_elegans		WBGENE00000885

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPIF (ENSG00000108179), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), PPIG (ENSG00000138398), CWC27 (ENSG00000153015), PPIB (ENSG00000166794), PPIC (ENSG00000168938), PPID (ENSG00000171497), PPIH (ENSG00000171960), PPIL6 (ENSG00000185250), PPIA (ENSG00000196262), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase A-like 4A — Q9Y536 (reviewed: Q9Y536)

Alternative names: Chromosome one-amplified sequence 2, Cyclophilin homolog overexpressed in liver cancer

All UniProt accessions (1): Q9Y536

UniProt curated annotations — full annotation on UniProt →

Function. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in brain, ovary and mammary gland. Moderately expressed in lung, salivary gland, kidney, skin, adipose tissue, intestine and spleen. Weakly expressed in skeletal muscle, liver and stomach. Expressed in pleiomorphic and undifferentiated liposarcomas, osteosarcomas and breast carcinomas.

Miscellaneous. It is one of six related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 1.

Similarity. Belongs to the cyclophilin-type PPIase family. PPIase A subfamily.

RefSeq proteins (1): NP_001137355* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
IPR024936	Cyclophilin-type_PPIase	Family
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily

Pfam: PF00160

Catalyzed reactions (Rhea), 1 shown:

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y536-F1	96.25	0.97

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_PROTEIN_MATURATION, chr1p11, GOBP_PROTEIN_FOLDING, ACEVEDO_LIVER_CANCER_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, CAMPS_COLON_CANCER_COPY_NUMBER_DN, GOMF_CIS_TRANS_ISOMERASE_ACTIVITY, GOMF_AMIDE_BINDING, GOMF_ISOMERASE_ACTIVITY, GOMF_CYCLOSPORIN_A_BINDING, MIR548V, MIR6750_5P, MIR6822_5P, QI_PBMC_ZOSTAVAX_AGE_50_75YO_CORRELATED_WITH_CONTRACTION_OF_VZV_SPECIFIC_T_CELLS_PEAK_TO_28DYAT_1DY_NEGATIVE

GO Biological Process (2): protein folding (GO:0006457), protein peptidyl-prolyl isomerization (GO:0000413)

GO Molecular Function (3): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), cyclosporin A binding (GO:0016018), isomerase activity (GO:0016853)

GO Cellular Component (2): cytoplasm (GO:0005737), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
peptidyl-proline modification	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1977 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIAL4A	NBPF12	Q5TAG4	986
PPIAL4A	PRSS38	A1L453	433
PPIAL4A	H2AZ1	P0C0S5	400
PPIAL4A	H2BC9	Q93079	371
PPIAL4A	NBPF11	Q86T75	351
PPIAL4A	NBPF14	Q5TI25	351
PPIAL4A	PITX2	Q99697	329
PPIAL4A	H1-5	P16401	326
PPIAL4A	TOP2B	Q02880	324
PPIAL4A	NBPF15	Q8N660	324
PPIAL4A	OTOP3	Q7RTS5	315
PPIAL4A	OTOP2	Q7RTS6	297
PPIAL4A	ACP6	Q9NPH0	256
PPIAL4A	TBPL1	P62380	251
PPIAL4A	TSPAN31	Q12999	247

IntAct

8 interactions, top by confidence:

A	B	Type	Score
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
SDHA	HMGB3	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
SDHA	NME2P1	psi-mi:“MI:0914”(association)	0.350
PPIAL4G	PPIAL4D	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): PPIAL4B (Affinity Capture-MS), PPIAL4B (Affinity Capture-MS), PPIAL4B (Affinity Capture-MS), PPIAL4B (Affinity Capture-MS), PPIAL4B (Affinity Capture-MS), PPIAL4B (Affinity Capture-MS), PPIAL4B (Affinity Capture-MS), PPIAL4B (Negative Genetic), PPIAL4B (Affinity Capture-MS), PPIAL4B (Affinity Capture-MS), PPIAL4B (Cross-Linking-MS (XL-MS)), PPIAL4B (Cross-Linking-MS (XL-MS)), PPIAL4B (Cross-Linking-MS (XL-MS)), PPIAL4B (Cross-Linking-MS (XL-MS)), PPIAL4B (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A075B759, A0A075B767, A0A0B4J2A2, F5H284, O00060, O43447, O74729, O94273, P0C1I0, P0C1I3, P0C1I5, P0C1I8, P0CP82, P0CP83, P0DN26, P0DN37, P17742, P23285, P24525, P25719, P52010, P52018, P62940, P84343, Q0P5D0, Q0ZQK7, Q0ZQK8, Q0ZQL0, Q0ZQL1, Q26516, Q26551, Q26565, Q27774, Q2TZ33, Q38867, Q38900, Q42406, Q4IPH4, Q4P6X6, Q4WCM6

Diamond homologs: A0A075B759, A0A075B767, A0A0B4J2A2, A0A0R0H9T5, A4FV72, D4AY02, F5H284, H2QII6, O00060, O49886, O93826, P0C1H7, P0C1H8, P0C1I2, P0C1I7, P0C1I8, P0C1I9, P0CP78, P0CP79, P0DN26, P0DN37, P10111, P10255, P14088, P14832, P14851, P17742, P18253, P21568, P21569, P22011, P24367, P24525, P25007, P25719, P29117, P30404, P30405, P34790, P34791

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

19 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

237 predictions. Top by Δscore:

Variant	Effect	Δscore
1:120889944:T:A	donor_gain	0.7600
1:120890044:TGTC:T	donor_gain	0.7600
1:120889862:C:T	donor_gain	0.7500
1:120889953:T:TA	donor_gain	0.7500
1:120889860:G:A	donor_gain	0.7300
1:120889998:AAA:A	donor_gain	0.7000
1:120889999:TAA:T	donor_gain	0.7000
1:120890045:TTGT:T	donor_gain	0.6900
1:120890046:CTTG:C	donor_gain	0.6900
1:120889998:AAAC:A	donor_gain	0.6800
1:120889971:G:C	donor_gain	0.6700
1:120890487:A:C	donor_gain	0.6700
1:120889956:AAAT:A	donor_gain	0.6100
1:120889969:A:AT	donor_gain	0.6100
1:120890012:C:CT	donor_gain	0.6100
1:120890192:C:T	donor_gain	0.5900
1:120889948:T:A	donor_gain	0.5800
1:120889969:AAC:A	donor_gain	0.5800
1:120890190:G:A	donor_gain	0.5800
1:120889955:AAT:A	donor_gain	0.5700
1:120889967:C:A	donor_gain	0.5700
1:120890176:C:CG	donor_gain	0.5700
1:120889934:AGAG:A	donor_gain	0.5600
1:120889968:AC:A	donor_gain	0.5600
1:120889983:T:TA	donor_gain	0.5600
1:120890150:TGGG:T	donor_gain	0.5600
1:120890174:GAC:G	donor_gain	0.5600
1:120890175:AGT:A	donor_gain	0.5600
1:120890009:C:A	donor_gain	0.5500
1:120890175:A:AC	donor_gain	0.5500

AlphaMissense

1104 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:120890205:T:C	F129L	0.811
1:120890207:T:A	F129L	0.811
1:120890207:T:G	F129L	0.811
1:120890154:T:C	F112L	0.808
1:120890156:T:A	F112L	0.808
1:120890156:T:G	F112L	0.808
1:120889998:T:C	F60L	0.791
1:120890000:T:A	F60L	0.791
1:120890000:T:G	F60L	0.791
1:120890067:T:C	F83L	0.787
1:120890069:T:A	F83L	0.787
1:120890069:T:G	F83L	0.787
1:120889839:T:C	F7L	0.752
1:120889841:T:A	F7L	0.752
1:120889841:T:G	F7L	0.752
1:120889926:T:C	F36L	0.739
1:120889928:T:A	F36L	0.739
1:120889928:T:G	F36L	0.739
1:120889977:T:C	F53L	0.729
1:120889979:T:A	F53L	0.729
1:120889979:T:G	F53L	0.729
1:120890019:T:C	F67L	0.715
1:120890021:C:A	F67L	0.715
1:120890021:C:G	F67L	0.715
1:120889956:T:C	F46L	0.707
1:120889958:T:A	F46L	0.707
1:120889958:T:G	F46L	0.707
1:120889893:T:C	F25L	0.678
1:120889895:T:A	F25L	0.678
1:120889895:T:G	F25L	0.678

dbSNP variants (sampled 300 via entrez): RS1156448519 (1:120889218 G>C), RS1156508139 (1:120888328 T>G), RS1158174015 (1:120888809 G>A,C), RS1158305788 (1:120890179 A>G), RS1158382158 (1:120889462 GA>G,GAA), RS1160377887 (1:120890730 G>A), RS1160494630 (1:120889849 T>C), RS1160635236 (1:120889299 G>A), RS1160756159 (1:120888406 C>A), RS1161244159 (1:120890259 T>C), RS1161614668 (1:120888035 AAAG>A), RS1162638822 (1:120889503 AAAGAAAGAAATT>A), RS1162867765 (1:120888901 C>T), RS1164430416 (1:120891001 G>T), RS1164536895 (1:120889904 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
chloropicrin	affects expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
Tunicamycin	decreases expression	2
beauvericin	affects cotreatment, decreases expression	1
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
enniatins	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Bucladesine	affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Methylcholanthrene	increases reaction, affects binding	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Medroxyprogesterone Acetate	affects cotreatment, decreases expression	1
Thapsigargin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.